Skip to main content

Advertisement

SpringerLink
Log in

Percorso di laboratorio raccomandato nella diagnosi, prognosi e follow-up delle gammopatie monoclonali

Recommended laboratory path for the diagnosis, prognosis and follow up of monoclonal gammopathies

  • Rassegna
  • Published:
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine

Riassunto

In Italia, l’elevata prevalenza delle gammopatie monoclonali nella popolazione adulta e l’alta cadenza con la quale si richiede l’elettroforesi delle proteine sieriche, per svariate esigenze cliniche, determinano due conseguenze. Da una parte è relativamente frequente il riscontro occasionale nella storia di un individuo di una componente monoclonale (CM) sierica, dall’altra si rende necessario inquadrare correttamente i dati laboratoristici e programmare successivamente esami diagnostici mirati e appropriati. Il gran numero di lavori scientifici pubblicato a livello internazionale negli ultimi 15 anni, soprattutto da ematologi clinici, ha attribuito un’importanza determinante ai test di laboratorio nella gestione dei pazienti con gammopatie monoclonali, ma non sempre ha dato indicazioni univoche e coerenti sulla scelta dei test di laboratorio da praticare nelle diverse situazioni cliniche e sulle modalità di esecuzione e d’interpretazione degli stessi. A questo proposito, il Gruppo di Studio “Proteine” della Società Italiana di Patologia Clinica e Medicina di Laboratorio (SIPMeL) ha considerato opportuno raccogliere in un documento una serie di “raccomandazioni” sull’utilizzo dei test di laboratorio, in particolare di quelli compresi nella disciplina Protidologia, nella diagnosi, prognosi e follow-up delle gammopatie monoclonali. In appendice vengono riportate note metodologiche riguardanti aspetti pre-analitici e analitici controversi, relativi all’esecuzione dei principali esami di laboratorio descritti nel testo.

Summary

In Italy, the high occurrence of monoclonal gammopathies in adults and the high frequency of requests for serum protein electrophoresis have two consequences. On one hand it is relatively frequent in a person’s history to come across a serum monoclonal component; on the other it is necessary to correctly frame the laboratory data and, consequently, plan the appropriate targeted lab tests. In the last fifteen years, the international scientific publications (mainly by clinical hematologists) have shown the great importance of lab testing in the management of patients with monoclonal gammopathies. However these studies have not always given coherent and precise indications on the appropriate choice of laboratory tests in different clinical situations, or how to correctly perform and interpret them. In this regard, the Study Group “Proteins” of the Italian Society of Clinical Pathology and Laboratory Medicine (SIPMeL) has collected in a document a series of “advices” on the use of laboratory tests in the diagnosis, prognosis and follow-up of monoclonal gammopathies, in particular those included in the branch that studies the plasma protein assays. The appendix shows methodological notes concerning controversial analytical and pre-analytical aspects of the execution of the main laboratory tests described in the paper.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Bibliografia

  1. International Myeloma Working Group (2003) Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121:749–757

    Article  Google Scholar 

  2. Durie BG, Salmon SE (1975) A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 36:842–854

    Article  CAS  PubMed  Google Scholar 

  3. Bence Jones H (1848) On a new substance occurring in the urine of a patient with mollities Ossium. Philos Trans R Soc 138:55–62

    Article  Google Scholar 

  4. Edelman GM, Gally JA (1962) The nature of Bence Jones protein: chemical similarities to polypeptide chains of myeloma globulins and normal \(\gamma\) globulins. J Exp Med 116:207–227

    Article  CAS  PubMed  Google Scholar 

  5. Solomon A (1986) Light chains immunoglobulin. Structural-genetic correlates. Blood 68:603–610

    CAS  PubMed  Google Scholar 

  6. AIRTUM Working Group (2011) I tumori in Italia. Rapporto 2011: la sopravvivenza dei pazienti oncologici in Italia. http://www.quotidianosanita.it/allegati/allegato7094573.pdf (Accesso 2 agosto 2016)

  7. Kyle RA, Rajkumar SV (2006) Monoclonal gammopathy of undetermined significance. Br J Haematol 134:573–589

    Article  CAS  PubMed  Google Scholar 

  8. Aguzzi F, Bergami MR, Gasparro C et al. (1992) Occurrence of monoclonal components in general practice: clinical implications. Eur J Haematol 48:192–195

    Article  CAS  PubMed  Google Scholar 

  9. Keren DF, Alexanian R, Goeken JA et al. (1999) Guidelines for clinical and laboratory evaluation of patients with monoclonal gammopathies. Arch Pathol Lab Med 123:106–107

    CAS  PubMed  Google Scholar 

  10. Milani P, Palladini G, Graziani MS et al. (2013) Componenti monoclonali piccole ma dannose. Biochimica Clinica 37:431–434

    Google Scholar 

  11. Merlini G (2012) Perchè è importante identificare e segnalare le piccole componenti monoclonali. Biochimica Clinica 36:25–28

    Google Scholar 

  12. Kyle RA, San-Miguel JF, Mateos MV et al. (2014) Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Hematol Oncol Clin North Am 28:775–790

    Article  PubMed  Google Scholar 

  13. Durie BG, Harousseau JL, Miguel JS et al. (2006) International uniform response criteria for multiple myeloma. Leukemia 20:1467–1473

    Article  CAS  PubMed  Google Scholar 

  14. Munshi NC, Anderson KC, Bergsagel PL et al. (2011) Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood 117:4696–4700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dispenzieri A, Kyle R, Merlini G et al. (2009) International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 23:215–224

    Article  CAS  PubMed  Google Scholar 

  16. Dimopoulos M, Kyle R, Fermand JP et al. (2011) Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood 117:4701–4705

    Article  CAS  PubMed  Google Scholar 

  17. NCCN Guidelinees. Multiple Myeloma. https://www.nccn.org/patients/guidelines/cancers.aspx#myeloma (Accesso 2 agosto 2016)

  18. Kyrtsonis MC, Vassilakopoulos TP, Kafasi N et al. (2007) Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma. Br J Haematol 137:240–243

    Article  CAS  PubMed  Google Scholar 

  19. Iwama K, Chihara D, Tsuda K et al. (2013) Normalization of free light chain kappa/lambda ratio is a robust prognostic indicator of favorable outcome in patients with multiple myeloma. Eur J Haematol 90:134–141

    Article  CAS  PubMed  Google Scholar 

  20. Snozek CL, Katzmann JA, Kyle RA et al. (2008) Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia 22:1933–1937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sthaneshwar P, Nadarajan V, Maniam JA et al. (2009) Serum free light chains: diagnostic and prognostic value in multiple myeloma. Clin Chem Lab Med 47:1101–1107

    Article  CAS  PubMed  Google Scholar 

  22. Abraham RS, Clark RJ, Bryant SC et al. (2002) Correlation of serum immunoglobulin free light chain quantification with urinary Bence Jones protein in light chain myeloma. Clin Chem 48:655–657

    CAS  PubMed  Google Scholar 

  23. Graziani MS, Merlini G, Petrini C (2001) Linee guida per la ricerca della proteina di Bence Jones. Biochimica Clinica 25:23–32

    Google Scholar 

  24. Graziani MS, Merlini GP, Petrini C, IFCC Committee on Plasma Proteins and the SIBioC Study Group on Proteins (2003) Guidelines for the analysis of Bence Jones Protein. Clin Chem Lab Med 41:338–346

    Article  CAS  PubMed  Google Scholar 

  25. Kyle RA (1999) sequence of testing for monoclonal gammopathies. Arch Pathol Lab Med 123:114–118

    CAS  PubMed  Google Scholar 

  26. Bird JM, Owen RG, D’Sa S et al (2014) Guidelines for the diagnosis and management of multiple myeloma. http://www.bcshguidelines.com/documents/MYELOMA_GUIDELINE_Feb_2014_for_BCSH.pdf (Accesso agosto 2016)

  27. Kyle RA, Durie BG, Rajkumar SV et al. (2010) Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia 24:1121–1127

    Article  CAS  PubMed  Google Scholar 

  28. Rajkumar SV, Dimopoulos MA, Palumbo A et al. (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15:e538–e548

    Article  PubMed  Google Scholar 

  29. Kyle RA, Therneau TM, Rajkumar SV (2002) A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 346:564–569

    Article  PubMed  Google Scholar 

  30. Kyle RA, Therneau TM, Rajkumar SV et al. (2006) Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 354:1362–1369

    Article  CAS  PubMed  Google Scholar 

  31. Owen RG, Treon SP, Al-Katib A et al. (2003) Clinicopathological definition of Waldenström’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenström’s Macroglobulinemia. Semin Oncol 30:110–115

    Article  PubMed  Google Scholar 

  32. Rajkumar SV, Kyle RA, Buadi FK (2010) Advances in the diagnosis, classification, risk stratification, and management of monoclonal gammopathy of undetermined significance: implications for recategorizing disease entities in the presence of evolving scientific evidence. Mayo Clin Proc 85:945–948

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kyle RA, Therneau TM, Rajkumar SV et al. (2004) Long-term follow-up of 241 patients with monoclonal gammopathy of undetermined significance: the original Mayo Clinic series 25 years later. Mayo Clin Proc 79:859–866

    Article  PubMed  Google Scholar 

  34. Cesana C, Klersy C, Barbarano L et al. (2002) Prognostic factors for malignant transformation in monoclonal gammopathy of undeterminated significance and smoldering myeloma. J Clin Oncol 20:1625–1634

    Article  PubMed  Google Scholar 

  35. Rajkumar SV, Kyle RA, Therneau TM et al. (2005) Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 106:812–817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Rosiñol L, Cibeira MT, Montoto S et al. (2007) Monoclonal gammopathy of undetermined significance: predictors of malignant transformation and recognition of an evolving type characterized by a progressive increase in M protein size. Mayo Clin Proc 82:428–434

    Article  PubMed  Google Scholar 

  37. Dispenzieri A, Katzmann JA, Kyle RA et al. (2010) Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet 15:1721–1728

    Article  Google Scholar 

  38. Eisele L, Dürig J, Hüttmann A et al. (2012) Prevalence and progression of monoclonal gammopathy of undetermined significance and light-chain MGUS in Germany. Ann Hematol 91:243–248

    Article  CAS  PubMed  Google Scholar 

  39. Rajkumar SV, Kyle RA, Therneau TM et al. (2004) Presence of monoclonal free light chains in the serum predicts risk of progression in monoclonal gammopathy of undetermined significance. Br J Haematol 127:308–310

    Article  CAS  PubMed  Google Scholar 

  40. Larsen JT, Kumar SK, Dispenzieri A et al. (2013) Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia 4:941–946

    Article  CAS  Google Scholar 

  41. Pérez-Persona E, Vidriales MB, Mateo G et al. (2007) New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood 110:2586–2592

    Article  PubMed  CAS  Google Scholar 

  42. Rossi F, Petrucci MT, Guffanti A et al. (2009) Proposal and validation of prognostic scoring systems for IgG and IgA monoclonal gammopathies of undetermined significance. Clin Cancer Res 15:4439–4445

    Article  CAS  PubMed  Google Scholar 

  43. Paiva B, Vidriales MB, Pérez JJ et al. (2009) GEM Multiparameter flow cytometry quantification of bone marrow plasma cells at diagnosis provides more prognostic information than morphological assessment in myeloma patients. Haematologica 94:1599–1602

    Article  PubMed  PubMed Central  Google Scholar 

  44. Pérez-Persona EL, Mateo G, García-Sanz R et al. (2010) Risk of progression in smouldering myeloma and monoclonal gammopathies of unknown significance: comparative analysis of the evolution of monoclonal component and multiparameter flow cytometry of bone marrow plasma cells. Br J Haematol 148:110–114

    Article  PubMed  Google Scholar 

  45. Paiva B, Almeida J, Pérez-Andrés M et al. (2010) Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders. Cytometry B Clin Cytom 78:239–252

    PubMed  Google Scholar 

  46. Agarwal A, Ghobrial IM (2013) Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: a review of the current understanding of epidemiology, biology, risk stratification, and management of myeloma precursor disease. Clin Cancer Res 19:985–994

    Article  PubMed  Google Scholar 

  47. Gregersen H, Mellemkjaer L, Ibsen JS et al. (2001) The impact of M-component type and immunoglobulin concentration on the risk of malignant transformation in patients with monoclonal gammopathy of undetermined significance. Haematologica 86:1172–1179

    CAS  PubMed  Google Scholar 

  48. Mailankody S, Pfeiffer RM, Kristinsson SY et al. (2011) Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS). Blood 118:4086–4092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Roeker LE, Larson DR, Kyle RA et al. (2013) Risk of acute leukemia and myelodysplastic syndromes in patients with monoclonal gammopathy of undetermined significance (MGUS): a population-based study of 17,315 patients. Leukemia 27:1391–1393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kyle RA, Remstein ED, Therneau TM et al. (2007) Clinical course and prognosis of smoldering (asyntomatic) multiple myeloma. N Engl J Med 356:2582–2590

    Article  CAS  PubMed  Google Scholar 

  51. Kyle RA, Rajkumar SV (2009) Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 23:3–9

    Article  CAS  PubMed  Google Scholar 

  52. Rajkumar SV, Larson D, Kyle RA (2011) Diagnosis of smoldering multiple myeloma. N Engl J Med 365:474–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Rajkumar SV, Merlini G, San Miguel JF (2012) Haematological cancer: redefining myeloma. Nat Rev Clin Oncol 9:494–496

    Article  PubMed  Google Scholar 

  54. Dispenzieri A, Stewart AK, Chanan-Khan A et al. (2013) Smoldering multiple myeloma requiring treatment: time for a new definition? Blood 122:4172–4181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Durie BG, Salmon SE (1975) A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 36:842–854

    Article  CAS  PubMed  Google Scholar 

  56. Ghobrial IM, Landgren O (2014) How I treat smoldering myeloma. Blood 124:3380–3388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Landgren O (2013) Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: biological insights and early treatment strategies. Hematology Am Soc Hematol Educ Program 2013:478–487

    PubMed  Google Scholar 

  58. Palumbo A, Avet-Loiseau H, Oliva S et al. (2015) Revised international staging system for multiple myeloma. A report from International Myeloma Working Group. J Clin Oncol 33:2863–2869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Landgren O, Kyle RA, Pfeiffer RM et al. (2009) Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 113:5412–5417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Greipp PR, San Miguel J, Durie BG et al. (2005) International staging system for multiple myeloma. J Clin Oncol 23:3412–3420

    Article  PubMed  Google Scholar 

  61. Maisnar V, Tichý M, Smolej L et al. (2007) Isotype class switching after transplantation in multiple myeloma. Neoplasma 54:225–228

    CAS  PubMed  Google Scholar 

  62. Alejandre ME, Madalena LB, Pavlovsky MA et al. (2010) Oligoclonal bands and immunoglobulin isotype switch during monitoring of patients with multiple myeloma and autologous hematopoietic cell transplantation: a 16-year experience. Clin Chem Lab Med 48:727–731

    Article  CAS  PubMed  Google Scholar 

  63. Sucak G, SuyanıE, Özkurt ZN et al. (2010) Abnormal protein bands in patients with multiple myeloma after haematopoietic stem cell transplantation: does it have a prognostic significance? Hematol Oncol 28:180–184

    Article  CAS  PubMed  Google Scholar 

  64. Wadhera RK, Kyle RA, Larson DR et al. (2011) Incidence, clinical course, and prognosis of secondary monoclonal gammopathy of undetermined significance in patients with multiple myeloma. Blood 118:2985–2987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Manson GV, Campagnaro E, Balog A et al. (2012) Secondary MGUS after autologous hematopoietic progenitor cell transplantation in plasma cell myeloma: a matter of undetermined significance. Bone Marrow Transplant 47:1212–1216

    Article  CAS  PubMed  Google Scholar 

  66. Schmitz MF, Otten HG, Franssen LE et al. (2014) Secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation in multiple myeloma. Haematologica 99:1846–1853

    Article  PubMed  PubMed Central  Google Scholar 

  67. Katzmann JA, Clark R, Sanders E et al. (1998) Prospective study of serum protein capillary zone electrophoresis and immunotyping of monoclonal proteins by immunosubtraction. Am J Clin Pathol 110:503–509

    Article  CAS  PubMed  Google Scholar 

  68. Bossuyt X (2003) Separation of serum proteins by automated capillary zone electrophoresis. Clin Chem Lab Med 41:762–772

    CAS  PubMed  Google Scholar 

  69. McCudden CR, Mathews SP, Hainsworth SA et al. (2008) Performance comparison of capillary and agarose gel electrophoresis for identification and characterization of monoclonal immunoglobulins. Am J Clin Pathol 129:451–458

    Article  CAS  PubMed  Google Scholar 

  70. Yang Z, Harrison K, Park YA et al. (2007) Performance of the Sebia Capillarys 2 for detection and immunotyping of serum monoclonal paraproteins. Am J Clin Pathol 128:293–299

    Article  CAS  PubMed  Google Scholar 

  71. Szymanowicz A, Doche C, Schemitick I (2008) A monoclonal immunoglobulin M not visible on the profile of serum capillary electrophoresis. Ann Biol Clin (Paris) 66:465–469

    CAS  Google Scholar 

  72. Zetterberg H, Nilsson-Ehle H (2004) False-negative result in the detection of an IgM monoclonal protein by capillary zone electrophoresis. Clin Chem 50:1878–1880

    Article  CAS  PubMed  Google Scholar 

  73. Gay-Bellile C, Bengoufa D, Houze P et al. (2003) Automated multicapillary electrophoresis for analysis of human serum proteins. Clin Chem 49:1909–1915

    Article  CAS  PubMed  Google Scholar 

  74. Wils J, Lavoinne A, Vaillant C (2013) Detecting a peak in fraction beta by capillary electrophoresis: interference due to iomeprol. Ann Biol Clin (Paris) 71:196–198

    CAS  Google Scholar 

  75. Lippi G, Daves M, Mattiuzzi C (2014) Interference of medical contrast media on laboratory testing. Biochem Med (Zagreb) 24:80–88

    Article  CAS  Google Scholar 

  76. Seaux L, Van Houcke S, Dumoulin E et al. (2014) Dual-wavelength recording, a simple algorithm to eliminate interferences due to UV-absorbing substances in capillary electrophoresis. Electrophoresis 35:2248–2252

    Article  CAS  PubMed  Google Scholar 

  77. Katzmann JA, Snyder MR, Rajkumar SV et al. (2011) Long-term biological variation of serum protein electrophoresis M-spike, urine M-spike, and monoclonal serum free light chain quantification: implications for monitoring monoclonal gammopathies. Clin Chem 57:1687–1692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Tate J, Caldwell G, Daly J et al. (2012) Recommendations for standardized reporting of protein electrophoresis in Australia and New Zealand. Ann Clin Biochem 49:242–256

    Article  CAS  PubMed  Google Scholar 

  79. Boyle EM, Fouquet G, Guidez S et al. (2014) IgA kappa/IgA lambda heavy/light chain assessment in the management of patients with IgA myeloma. Cancer 120:3952–3957

    Article  CAS  PubMed  Google Scholar 

  80. Ruggeri M, Bottan F, Chiarugi P et al. (2001) Linee guida per la diagnostica ed il monitoraggio delle gammopatie monoclonali. RivMed Lab/JLM 2:68–71

    Google Scholar 

  81. Bergón E, Miranda I, Miravalles E (2005) Linearity and detection limit in the measurement of serum M-protein with the capillary zone electrophoresis system Capillarys. Clin Chem Lab Med 43:721–723

    Article  PubMed  CAS  Google Scholar 

  82. Mussap M, Pietrogrande F, Ponchia S et al. (2006) Measurement of serum monoclonal components: comparison between densitometry and capillary zone electrophoresis. Clin Chem Lab Med 44:609–611

    Article  CAS  PubMed  Google Scholar 

  83. O’Connell TX, Horita TJ, Kasravi B (2005) Understanding and interpreting serum protein electrophoresis. Am Fam Physician 71:105–112

    PubMed  Google Scholar 

  84. Keren DF, Schroeder L (2016) Challenges of measuring monoclonal proteins in serum. Clin Chem Lab Med 54:947–961

    Article  CAS  PubMed  Google Scholar 

  85. Riches PG, Sheldon J, Smith AM et al. (1991) Overestimation of monoclonal immunoglobulin by immunochemical methods. Ann Clin Biochem 28:253–259

    Article  PubMed  Google Scholar 

  86. Schild C, Wermuth B, Trapp-Chiappini D et al. (2008) Reliability of M protein quantification: comparison of two peak integration methods on Capillarys 2. Clin Chem Lab Med 46:876–877

    Article  CAS  PubMed  Google Scholar 

  87. Keren DF (2012) Protein electrophoresis in clinical diagnosis. ASCP Press, Chicago

    Book  Google Scholar 

  88. Katzmann JA, Keren DF (2016) Strategy for detecting and following monoclonal gammopathies. In: Detrick B, Schmitz J, Hamilton R (eds) Manual of molecular and clinical laboratory immunology, 8th edn. ASM Press, Washington (DC), pp 112–124. doi:10.1128/9781555818722

    Google Scholar 

  89. Wunsch C (2015) Extending capillary zone electrophoresis (CZE) of serum proteins. Clin Chem 61:5212

    Google Scholar 

  90. Ludwig H, Miguel JS, Dimopoulos MA et al. (2014) International myeloma working group recommendations for global myeloma care. Leukemia 28:981–992

    Article  CAS  PubMed  Google Scholar 

  91. Eckold J, Poenisch W, Drogies T et al. (2014) Analytical performance and diagnostic potential of immunoassays determining intact immunoglobulin kappa/lambda ratios in monoclonal gammopathies. Clin Lab 60:1491–1500

    Article  CAS  PubMed  Google Scholar 

  92. Batinić J, Perić Z, Šegulja D et al. (2015) Immunoglobulin heavy/light chain analysis enhances the detection of residual disease and monitoring of multiple myeloma patients. Croat Med J 56:263–271

    Article  PubMed  PubMed Central  Google Scholar 

  93. Katzmann JA, Willrich MA, Kohlhagen MC et al. (2015) Monitoring IgA multiple myeloma: immunoglobulin heavy/light chain assays. Clin Chem 61:360–367

    Article  CAS  PubMed  Google Scholar 

  94. Paolini L, Di Noto G, Maffina F et al. (2015) Comparison of Hevylite™ IgA and IgG assay with conventional techniques for the diagnosis and follow-up of plasma cell dyscrasia. Ann Clin Biochem 52:337–345

    Article  CAS  PubMed  Google Scholar 

  95. Bergón E, Miravalles E (2008) Estimation of serum M-protein concentration from polyclonal immunoglobulins: an alternative to serum protein electrophoresis and standard immunochemical procedures. Clin Chem Lab Med 46:1156–1162

    Article  PubMed  CAS  Google Scholar 

  96. Murray DL, Ryu E, Snyder MR et al. (2009) Quantitation of serum monoclonal proteins: relationship between agarose gel electrophoresis and immunonephelometry. Clin Chem 55:1523–1529

    Article  CAS  PubMed  Google Scholar 

  97. Barnidge DR, Dasari S, Ramirez-Alvarado M et al. (2014) Phenotyping polyclonal kappa and lambda light chain molecular mass distributions in patient serum using mass spectrometry. J Proteome Res 13:5198–5205

    Article  CAS  PubMed  Google Scholar 

  98. Mills JR, Barnidge DR, Murray DL (2015) Detecting monoclonal immunoglobulins in human serum using mass spectrometry. Methods 81:56–65

    Article  CAS  PubMed  Google Scholar 

  99. Rajkumar SV, Harousseau JL, Durie B et al. (2011) Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood 117:4691–4695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bakshi NA, Gulbranson R, Garstka D et al. (2005) Serum free light chain (FLC) measurement can aid capillary zone electrophoresis in detecting subtle FLC-producing M proteins. Am J Clin Pathol 124:214–218

    Article  CAS  PubMed  Google Scholar 

  101. Mussap M, Ponchia S, Zaninotto M et al. (2006) Evaluation of a new capillary zone electrophoresis system for the identification and typing of Bence Jones protein. Clin Biochem 39:152–159

    Article  CAS  PubMed  Google Scholar 

  102. Bossuyt X, Bogaerts A, Schiettekatte G et al. (1998) Detection and classification of paraproteins by capillary immunofixation/subtraction. Clin Chem 44:760–764

    CAS  PubMed  Google Scholar 

  103. Bossuyt X, Schiettekatte G, Bogaerts A et al. (1998) Serum protein electrophoresis by CZE 2000 clinical capillary electrophoresis system. Clin Chem 44:749–759

    CAS  PubMed  Google Scholar 

  104. Smalley DL, Mayer RP, Bugg MF (2000) Capillary zone electrophoresis compared with agarose gel and immunofixation electrophoresis. Am J Clin Pathol 114:487–488

    CAS  PubMed  Google Scholar 

  105. Cornell FN, McLachlan R (1985) Isoelectric focusing in the investigation of gammopathies. In: Biegler B (ed) Advanced electrophoretic techniques for protein investigation in clinical diagnosis. Australian association of clinical biochemists monograph series. AACB, Sydney, pp 31–37

    Google Scholar 

  106. Beetham R (2000) Detection of Bence-Jones protein in practice. Ann Clin Biochem 37:563–570

    Article  CAS  PubMed  Google Scholar 

  107. Salomo M, Gimsing P, Nielsen LB (2002) Simple method for quantification of Bence Jones proteins. Clin Chem 48:2202–2207

    CAS  PubMed  Google Scholar 

  108. Bird J, Behrens J, Westin J et al. (2009) UK Myeloma Forum (UKMF) and Nordic Myeloma Study Group (NMSG): guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol 147:22–42

    Article  CAS  PubMed  Google Scholar 

  109. Harrison HH (1991) The ‘ladder light chain’ or ‘pseudo-oligoclonal’ pattern in urinary immunofixation electrophoresis (IFE) studies: a distinctive IFE pattern and an explanatory hypothesis relating it to free polyclonal light chains. Clin Chem 37:1559–1564

    CAS  PubMed  Google Scholar 

  110. MacNamara EM, Aguzzi F, Petrini C et al. (1991) Restricted electrophoretic heterogeneity of immunoglobulin light chains in urine: a cause for confusion with Bence Jones protein. Clin Chem 37:1570–1574

    CAS  PubMed  Google Scholar 

  111. Bailey EM, McDermott TJ, Bloch KJ (1993) The urinary light-chain ladder pattern. A product of improved methodology that may complicate the recognition of Bence Jones proteinuria. Arch Pathol Lab Med 117:707–710

    CAS  PubMed  Google Scholar 

  112. Levinson SS, Keren DF (1994) Free light chains of immunoglobulins: clinical laboratory analysis. Clin Chem 40:1869–1878

    CAS  PubMed  Google Scholar 

  113. Attaelmannan M, Levinson SS (2000) Understanding and identifying monoclonal gammopathies. Clin Chem 46:1230–1238

    CAS  PubMed  Google Scholar 

  114. Cornell FN (2009) Isoelectric focusing, blotting and probing methods for detection and identification of monoclonal proteins. Clin Biochem Rev 30:123–130

    PubMed  PubMed Central  Google Scholar 

  115. Gertz MA, Comenzo R, Falk RH et al. (2005) Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th international symposium on amyloid and amyloidosis, tours, France, 18–22 April 2004. Am J Hematol 79:319–328

    Article  PubMed  Google Scholar 

Download references

Ringraziamenti

Hanno collaborato alla realizzazione di questo documento, partecipando alla revisione del lavoro, i seguenti componenti del Gruppo di Studio Proteine della Società Italiana di Patologia Clinica e Medicina di Laboratorio:

– Dott.ssa Fiorella Bottan, Azienda Ospedaliera San Giovanni Addolorata, Roma, Italia.

– Dott.ssa Isabella Oliviero, Marilab, Roma, Italia.

Author information

Authors and Affiliations

  1. Azienda Ospedaliera Universitaria, Salerno, Italia

    Luigi Cinquanta

  2. Servizio di Patologia Clinica ASST-Garda, Gavardo, BS, Italia

    Marco Tani

  3. ISMETT, Palermo, Italia

    Maria Concetta Sorrentino

  4. Azienda Sanitaria Universitaria Integrata, Trieste, Italia

    Maria Paola Simula

  5. Ospedale Gaslini, Genova, Italia

    Salvatore Mangraviti

  6. Azienda Ospedaliera, Desenzano sul Garda, BS, Italia

    Bruno Milanesi

  7. Ospedale Buccheri La Ferla FBF, Palermo, Italia

    Ignazio Brusca

Authors
  1. Luigi Cinquanta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marco Tani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Concetta Sorrentino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Paola Simula
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Salvatore Mangraviti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bruno Milanesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ignazio Brusca
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luigi Cinquanta.

Ethics declarations

Conflitti di interesse

Nessuno.

Studi condotti su esseri umani e animali

Per questo tipo di studio non è richiesto l’inserimento di alcuna dichiarazione relativa agli studi effettuati su esseri umani e animali.

Consenso informato

Per questo tipo di studio non è richiesto l’inserimento di alcuna dichiarazione relativa al consenso informato.

Additional information

Per il Gruppo di Studio Proteine della Società Italiana di Patologia Clinica e Medicina di Laboratorio.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cinquanta, L., Tani, M., Sorrentino, M.C. et al. Percorso di laboratorio raccomandato nella diagnosi, prognosi e follow-up delle gammopatie monoclonali. Riv Ital Med Lab 13, 10–23 (2017). https://doi.org/10.1007/s13631-016-0130-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13631-016-0130-x

Parole chiave

Keywords

Search

Navigation